LILRB4
Leukocyte immunoglobulin-like receptor subfamily B member 4 is a protein that in humans is encoded by the LILRB4 gene.[5][6][7]
This gene is a member of the leukocyte immunoglobulin-like receptor (LIR) family, which is found in a gene cluster at chromosomal region 19q13.4. The encoded protein belongs to the subfamily B class of LIR receptors which contain two or four extracellular immunoglobulin domains, a transmembrane domain, and two to four cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs). The receptor is expressed on monocytic cells and transduces a negative signal that inhibits stimulation of an immune response. The receptor can also function in antigen capture and presentation. It is thought to control inflammatory responses and cytotoxicity to help focus the immune response and limit autoreactivity. The expression of LILRB4 on monocytic myeloid leukemia cells supports infiltration and inhibits T cell proliferation. Multiple transcript variants encoding different isoforms have been found for this gene.[7]
References
- ENSG00000186818, ENSG00000276042, ENSG00000278279, ENSG00000278555 GRCh38: Ensembl release 89: ENSG00000275730, ENSG00000186818, ENSG00000276042, ENSG00000278279, ENSG00000278555 - Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000112023 - Ensembl, May 2017
- "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- Cella M, Dohring C, Samaridis J, Dessing M, Brockhaus M, Lanzavecchia A, Colonna M (June 1997). "A Novel Inhibitory Receptor (ILT3) Expressed on Monocytes, Macrophages, and Dendritic Cells Involved in Antigen Processing". J Exp Med. 185 (10): 1743–51. doi:10.1084/jem.185.10.1743. PMC 2196312. PMID 9151699.
- Samaridis J, Colonna M (April 1997). "Cloning of novel immunoglobulin superfamily receptors expressed on human myeloid and lymphoid cells: structural evidence for new stimulatory and inhibitory pathways". Eur J Immunol. 27 (3): 660–5. doi:10.1002/eji.1830270313. PMID 9079806. S2CID 2212182.
- "Entrez Gene: LILRB4 leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains), member 4".
- Wang LL, Blasioli J, Plas DR, Thomas ML, Yokoyama WM (1999). "Specificity of the SH2 domains of SHP-1 in the interaction with the immunoreceptor tyrosine-based inhibitory motif-bearing receptor gp49B". Journal of Immunology. 162 (3): 1318–23. PMID 9973385.
- Zurli V, Wimmer G, Cattaneo F, Candi V, Cencini E, Gozzetti A, Raspadori D, Campoccia G, Sanseviero F, Bocchia M, Baldari CT, Kabanova A (2017). "Ectopic ILT3 controls BCR-dependent activation of Akt in B-cell chronic lymphocytic leukemia". Blood. 130 (18): 2006–2017. doi:10.1182/blood-2017-03-775858. PMID 28931525.
10. Deng M, Gui X, Kim J, Xie L, Chen W, Li Z, He L, Chen Y, Chen H, Luo W, Lu Z, Xie J, Churchill H, Xu Y, Zhou Z, Wu G, Yu C, John S, Hirayasu K, Nguyen N, Liu X, Huang F, Li L, Deng H, Tang H, Sadek AH, Zhang L, Huang T, Zou Y, Chen B, Zhu H, Arase H, Xia N, Jiang Y, Collins R, You MJ, Homsi J, Unni N, Lewis C, Chen GQ, Fu YX, Liao XC, An Z, Zheng J, Zhang N, Zhang CC. 2018. LILRB4 signaling in leukemia cells mediates T cell suppression and tumor infiltration. Nature. 562(7728):605-609
11. John S, Chen H, Deng M, Gui X, Wu G, Chen W, Li Z, Zhang N, An Z, Zhang CC. 2018. A novel anti-LILRB4 CAR-T cell for the treatment of monocytic AML. Molecular Therapy. 26(10):2487-2495
12. Gui X, Deng M, Song H, Chen Y, Xie J, Li Z, He L, Huang F, Xu Y, Anami Y, Yu H, Yu C, Li L, Yuan Z, Xu X, Wang Q, Chai Y, Huang T, Shi Y, Tsuchikama K, Liao XC, Xia N, Gao GF, Zhang N, Zhang C, An Z. 2019. Disrupting LILRB4/APOE interaction by an efficacious humanized antibody reverses T cell suppression and blocks AML development. Cancer Immunology Research. 7(8):1244-1257.
Further reading
- Suciu-Foca N, Cortesini R (2007). "Central role of ILT3 in the T suppressor cell cascade". Cell. Immunol. 248 (1): 59–67. doi:10.1016/j.cellimm.2007.01.013. PMID 17923119.
- Arm JP, Nwankwo C, Austen KF (1997). "Molecular identification of a novel family of human Ig superfamily members that possess immunoreceptor tyrosine-based inhibition motifs and homology to the mouse gp49B1 inhibitory receptor". J. Immunol. 159 (5): 2342–9. PMID 9278324.
- Kuroiwa A, Yamashita Y, Inui M, et al. (1998). "Association of tyrosine phosphatases SHP-1 and SHP-2, inositol 5-phosphatase SHIP with gp49B1, and chromosomal assignment of the gene". J. Biol. Chem. 273 (2): 1070–4. doi:10.1074/jbc.273.2.1070. PMID 9422771.
- Borges L, Hsu ML, Fanger N, et al. (1998). "A family of human lymphoid and myeloid Ig-like receptors, some of which bind to MHC class I molecules". J. Immunol. 159 (11): 5192–6. PMID 9548455.
- Torkar M, Norgate Z, Colonna M, et al. (1999). "Isotypic variation of novel immunoglobulin-like transcript/killer cell inhibitory receptor loci in the leukocyte receptor complex". Eur. J. Immunol. 28 (12): 3959–67. doi:10.1002/(SICI)1521-4141(199812)28:12<3959::AID-IMMU3959>3.0.CO;2-2. PMID 9862332.
- Wang LL, Blasioli J, Plas DR, et al. (1999). "Specificity of the SH2 domains of SHP-1 in the interaction with the immunoreceptor tyrosine-based inhibitory motif-bearing receptor gp49B". J. Immunol. 162 (3): 1318–23. PMID 9973385.
- Wilson MJ, Torkar M, Haude A, et al. (2000). "Plasticity in the organization and sequences of human KIR/ILT gene families". Proc. Natl. Acad. Sci. U.S.A. 97 (9): 4778–83. Bibcode:2000PNAS...97.4778W. doi:10.1073/pnas.080588597. PMC 18309. PMID 10781084.
- Heinzmann A, Blattmann S, Forster J, et al. (2000). "Common polymorphisms and alternative splicing in the ILT3 gene are not associated with atopy". Eur. J. Immunogenet. 27 (3): 121–7. doi:10.1046/j.1365-2370.2000.00214.x. PMID 10940079.
- Liu WR, Kim J, Nwankwo C, et al. (2000). "Genomic organization of the human leukocyte immunoglobulin-like receptors within the leukocyte receptor complex on chromosome 19q13.4". Immunogenetics. 51 (8–9): 659–69. doi:10.1007/s002510000183. PMID 10941837. S2CID 23687483.
- Young NT, Canavez F, Uhrberg M, et al. (2001). "Conserved organization of the ILT/LIR gene family within the polymorphic human leukocyte receptor complex". Immunogenetics. 53 (4): 270–8. doi:10.1007/s002510100332. PMID 11491530. S2CID 2819935.
- Chang CC, Ciubotariu R, Manavalan JS, et al. (2002). "Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4". Nat. Immunol. 3 (3): 237–43. doi:10.1038/ni760. PMID 11875462. S2CID 35400503.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- LeMaoult J, Zafaranloo K, Le Danff C, Carosella ED (2005). "HLA-G up-regulates ILT2, ILT3, ILT4, and KIR2DL4 in antigen presenting cells, NK cells, and T cells". FASEB J. 19 (6): 662–4. doi:10.1096/fj.04-1617fje. PMID 15670976. S2CID 24608530.
- Garner LI, Salim M, Mohammed F, Willcox BE (2006). "Expression, purification, and refolding of the myeloid inhibitory receptor leukocyte immunoglobulin-like receptor-5 for structural and ligand identification studies". Protein Expr. Purif. 47 (2): 490–7. doi:10.1016/j.pep.2005.11.020. PMID 16406677.
- Kim-Schulze S, Seki T, Vlad G, et al. (2006). "Regulation of ILT3 gene expression by processing of precursor transcripts in human endothelial cells". Am. J. Transplant. 6 (1): 76–82. doi:10.1111/j.1600-6143.2005.01162.x. PMID 16433759. S2CID 7662795.
- Kim-Schulze S, Scotto L, Vlad G, et al. (2006). "Recombinant Ig-like transcript 3-Fc modulates T cell responses via induction of Th anergy and differentiation of CD8+ T suppressor cells". J. Immunol. 176 (5): 2790–8. doi:10.4049/jimmunol.176.5.2790. PMID 16493035.
- Vlad G, Liu Z, Zhang QY, et al. (2007). "Immunosuppressive activity of recombinant ILT3". Int. Immunopharmacol. 6 (13–14): 1889–94. doi:10.1016/j.intimp.2006.07.017. PMID 17161342.
External links
- LILRB4+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
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